An open label two-stage study of orally administered BKM120 in patients with metastatic non-small cell lung cancer with activated PI3K pathway

• Conditions: Adult patients with metastatic NSCLC with activated PI3Kpathway.; MedDRA version: 14.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-024011-14-DE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05-10
• Last Update Posted: 25 January 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

1. Patient has signed the general Informed Consent Form (ICF) prior to any screening
procedures being performed
2. Patient is = 18 years of age on the day of consent signature
3. Patient has a histologically confirmed diagnosis of NSCLC with activated PI3K pathway
as defined by PIK3CA mutation and/or PTEN mutation an/or PTEN Negative (<10%
protein expression by IHC)
4. Note: a representative archival or fresh tumor biopsy must be available for shipping to a Novartis designated lab for molecular profiling
5. Patient has experienced objective progressive disease after the prior systemic
antineoplastic treatment(s) for advanced NSCLC is/are required as follows:
a. Group 1: Diagnosis of squamous NSCLC that progressed after one prior systemic
platinum based chemotherapy-line for metastatic disease
b. Group 2: Diagnosis of non-squamous NSCLC that progressed after one to two prior systemic antineoplastic therapy lines for metastatic disease
6. A representative archival or fresh tumor biopsy must be available for shipping to a
Novartis designated laboratory for profiling (See Section 6.1.8.3.1)
7. Patient has measurable and/or non-measurable disease as per RECIST 1.1 criteria
(Appendix 8)
8. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status = 2
9. Patient has adequate bone marrow and organ function as defined by the following
laboratory values:
• Absolutely Neutrophil Count (ANC) = 1.5 x 109/L
• Platelets = 100 x 109/L
• Hemoglobin = 9.0 g/dL
• INR = 2
• Potassium, calcium, magnesium within normal limits for the institution
• Serum Creatinine = 1.5 x ULN and creatinine clearance > 45 mL/min (refer to Section5.1.2.3 for calculation formula)
• Total Serum Bilirubin within normal range (or = 1.5 x ULN if liver metastases are
present, or total bilirubin = 3.0 x ULN with direct bilirubin within normal range in
patients with well documented Gilbert’s Syndrome)
• AST and ALT = ULN or < 3.0 x ULN if liver metastases are present
• Fasting plasma glucose (FPG) = 120 mg/dL or = 6.7 mmol/L

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Patient has received previous treatment with PI3K inhibitors
2. Patient in Stage 2 only:
a. Squamous Patients: previous treatment with docetaxel
b. Nonsquamous Patients: previous treatment with docetaxel and pemetrexed
3. Patient with squamous NSCLC has received more than one line of chemotherapy
treatment for metastatic disease; patient with non-squamous NSCLC has received more than two lines of systemic antineoplastic treatment for metastatic disease (for definition of prior lines of therapy please refer to inclusion criterion 4)
4. Patient with uncontrolled or symptomatic CNS metastases
• Patients with controlled and asymptomatic CNS metastases may participate in this
trial. The patient must have completed any prior treatment for CNS metastases = 28
days (must include radiotherapy and/or surgery) and, if on corticosteroid therapy,
should be receiving a stable low dose (e.g. dexamethasone 4 mg or equivalent dose of another corticosteroid for at least 14 days before start of study treatment)
5. Patient with a concurrent malignancy or malignancy within 5 years of study enrollment,(with the exception of adequately treated, basal or squamous cell carcinoma, nonmelanomatous skin cancer or curatively resected cervical cancer)
6. Patient who have not recovered to grade 1 or better from any adverse events (except alopecia) related to previous antineoplastic therapy before screening procedures are initiated
7. Patient has any of the following mood disorders as judged by the Investigator or a
Psychiatrist, or meets the cut-off score of = 10 in the PHQ-9 or a cut-off of = 15 in the GAD-7 mood scale, respectively, or selects a positive response of ‘1, 2, 3’ to question
number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the total score of the PHQ-9)
• Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
• = CTCAE grade 3 anxiety
8. Patient is concurrently using any other approved or investigational antineoplastic agent
9. Patient has received therapeutic radiotherapy = 28 days prior to starting study drug or has not recovered from side effects of such therapy
10. Patient has had major surgery within 28 days prior to starting study drug or who have not recovered from major side effects
11. Patient has poorly controlled diabetes mellitus (HbA1c > 8 %)
12. Patient has active cardiac disease
13. Patient has history of cardiac dysfunction
14. Patient is currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
15. Patient has impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
16. Patient receiving chronic treatment with steroids or another immunosuppressive agent. Patients with previously treated brain metastases, who are on a stable low dose corticosteroids treatment (e.g.,dexamethasone 4 mg/day or other steroids equivalent dose) for at least 14 days before start of study treatment, are eligible.
17. Patient has any other concurrent sev

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of BKM120 based on Progression Free Survival (PFS) as<br>measured using RECIST criteria,in metastatic NSCLC patientswith activated PI3K pathway<br>;Secondary Objective: To determine Objective Response Rate (ORR)<br>To determine Time to Response (TTR)<br>To determine Duration of Response<br>To determine Disease Control Rate (DCR)<br>To determine Overall Survival (OS)<br>To characterize the Safety;Primary end point(s): PFS per RECIST 1.1<br>12 week PFS rate (patients who progressed, died or discontinued before 12 weeks of observation are counted as failure; other cases are reported as success)